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Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone

Colorectal cancer (CRC), the third most prevalent cancer globally, presents formidable hurdles in treatment owing to factors such as therapeutic resistance and genetic mutations affecting primary drug targets. 2-methoxy-6-undecyl-1,4-benzoquinone (BQ), derived from Ardisia crispa roots, has emerged...

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Main Authors: Abd Rahman, Noor Izzah, Tham, Chau Ling, Abd Hamid @ Abdul Razak, Roslida
Format: Article
Language:English
Published: Elsevier Ireland 2024
Online Access:http://psasir.upm.edu.my/id/eprint/113669/1/113669.pdf
http://psasir.upm.edu.my/id/eprint/113669/
https://www.sciencedirect.com/science/article/pii/S0009279724002977
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spelling my.upm.eprints.1136692024-11-26T07:28:54Z http://psasir.upm.edu.my/id/eprint/113669/ Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone Abd Rahman, Noor Izzah Tham, Chau Ling Abd Hamid @ Abdul Razak, Roslida Colorectal cancer (CRC), the third most prevalent cancer globally, presents formidable hurdles in treatment owing to factors such as therapeutic resistance and genetic mutations affecting primary drug targets. 2-methoxy-6-undecyl-1,4-benzoquinone (BQ), derived from Ardisia crispa roots, has emerged as a potent anti-inflammatory and anti-angiogenic compound with substantial potential, as evidenced by previous studies. This study aimed to explore the potential of BQ in suppressing angiogenesis and metastasis in the human CRC cell lines LoVo and HCT116. Various in vitro and in silico studies have been conducted to elucidate the potential pathway(s) of BQ. BQ was highly cytotoxic, with an IC50 of 7.01±0.6 µM in HCT116 and 9.58±0.8 µM in LoVo cells. Moreover, BQ induced notable apoptotic activity and suppressed migration, invasion, and adhesion in both cell lines. The inhibition of MMP-2 suggests the potential of BQ to impede extracellular matrix degradation and CRC cell metastasis. BQ inhibits the expression of key proteins involved in angiogenesis and metastasis, including VEGF-A, VEGF-C, BRAF, ERK, KRAS, PI3K, and AKT. Molecular docking simulations illustrated the robust binding of BQ to CRC protein receptors. BQ holds promise in impeding CRC progression by targeting angiogenesis and metastasis, particularly through inhibition of the KRAS/BRAF/ERK and KRAS/PI3K/AKT signaling pathways. Keywords: Colorectal cancer; Angiogenesis; Metastasis; 2-methoxy-6-undecyl-1,4-benzoquinone; VEGF; KRAS; in silico Elsevier Ireland 2024 Article PeerReviewed text en cc_by_nc_nd_4 http://psasir.upm.edu.my/id/eprint/113669/1/113669.pdf Abd Rahman, Noor Izzah and Tham, Chau Ling and Abd Hamid @ Abdul Razak, Roslida (2024) Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone. Chemico-Biological Interactions, 399. art. no. 111151. pp. 1-11. ISSN 0009-2797; eISSN: 1872-7786 https://www.sciencedirect.com/science/article/pii/S0009279724002977 10.1016/j.cbi.2024.111151
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Colorectal cancer (CRC), the third most prevalent cancer globally, presents formidable hurdles in treatment owing to factors such as therapeutic resistance and genetic mutations affecting primary drug targets. 2-methoxy-6-undecyl-1,4-benzoquinone (BQ), derived from Ardisia crispa roots, has emerged as a potent anti-inflammatory and anti-angiogenic compound with substantial potential, as evidenced by previous studies. This study aimed to explore the potential of BQ in suppressing angiogenesis and metastasis in the human CRC cell lines LoVo and HCT116. Various in vitro and in silico studies have been conducted to elucidate the potential pathway(s) of BQ. BQ was highly cytotoxic, with an IC50 of 7.01±0.6 µM in HCT116 and 9.58±0.8 µM in LoVo cells. Moreover, BQ induced notable apoptotic activity and suppressed migration, invasion, and adhesion in both cell lines. The inhibition of MMP-2 suggests the potential of BQ to impede extracellular matrix degradation and CRC cell metastasis. BQ inhibits the expression of key proteins involved in angiogenesis and metastasis, including VEGF-A, VEGF-C, BRAF, ERK, KRAS, PI3K, and AKT. Molecular docking simulations illustrated the robust binding of BQ to CRC protein receptors. BQ holds promise in impeding CRC progression by targeting angiogenesis and metastasis, particularly through inhibition of the KRAS/BRAF/ERK and KRAS/PI3K/AKT signaling pathways. Keywords: Colorectal cancer; Angiogenesis; Metastasis; 2-methoxy-6-undecyl-1,4-benzoquinone; VEGF; KRAS; in silico
format Article
author Abd Rahman, Noor Izzah
Tham, Chau Ling
Abd Hamid @ Abdul Razak, Roslida
spellingShingle Abd Rahman, Noor Izzah
Tham, Chau Ling
Abd Hamid @ Abdul Razak, Roslida
Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
author_facet Abd Rahman, Noor Izzah
Tham, Chau Ling
Abd Hamid @ Abdul Razak, Roslida
author_sort Abd Rahman, Noor Izzah
title Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_short Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_full Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_fullStr Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_full_unstemmed Inhibition of angiogenesis and metastasis in colorectal cancer cell lines through KRAS-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
title_sort inhibition of angiogenesis and metastasis in colorectal cancer cell lines through kras-associated signaling pathways by 2-methoxy-6-undecyl-1,4-benzoquinone
publisher Elsevier Ireland
publishDate 2024
url http://psasir.upm.edu.my/id/eprint/113669/1/113669.pdf
http://psasir.upm.edu.my/id/eprint/113669/
https://www.sciencedirect.com/science/article/pii/S0009279724002977
_version_ 1817844679450820608
score 13.244413

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